Influence of GluN2 subunit identity on NMDA receptor function.
Influence of GluN2 subunit identity on NMDA receptor function.
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Glun2亚基身份对NMDA受体功能的影响。
DOI：
10.1016/j.neuropharm.2013.01.016
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发表时间：
2013-11
影响因子：
4.7
通讯作者：
Hardingham GE
中科院分区：
文献类型：
--
作者：
Wyllie DJ;Livesey MR;Hardingham GE
N-甲基-d-天冬氨酸受体（NMDAR）是由主要兴奋性神经递质L-谷氨酸激活的配体门控离子通道（“离子型”受体）。虽然经常使用术语“NMDAR”，但它掩盖了这类受体中包含其性质既相似又不同的成员的事实。这种异质性从NMDAR功能特性的早期电生理学、药理学和生物化学评估中显而易见，虽然这种异质性的分子基础已经花了很多年来阐明，但它从一开始就表明NMDAR表型的多样性可以使该受体家族在哺乳动物中枢神经系统中发挥多种功能。在这篇综述中，我们强调了一些最近的研究，已经确定了结构元件内的GluN 2亚基，有助于NMDAR的异质性生物物理特性，考虑为什么最近描述的一些新的药理学工具可能允许更好地识别天然NMDAR亚型，研究NMDAR亚型对长时程增强和长时程增强的诱导有不同贡献的证据。术语抑郁症，并讨论如何通过使用嵌合蛋白质的额外的见解已经获得的帐户NMDAR亚型依赖性的生理和病理生理信号。这篇文章是题为“谷氨酸受体依赖的突触可塑性”的特刊的一部分。综述了GluN 2亚基对NMDAR功能特性的控制。评估决定NMDAR异质性的GluN 2亚基的结构元件。考虑作用于NMDAR的正构和变构配体的效用。NMDAR C-末端结构域作为一种新的治疗靶点的潜力进行了讨论。
N-methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels (‘ionotropic’ receptors) activated by the major excitatory neurotransmitter, l-glutamate. While the term ‘the NMDAR’ is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar. This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system. In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological signalling. This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’. ► Reviews the control of NMDAR functional properties by GluN2 subunits. ► Assesses structural elements of GluN2 subunits that determine NMDAR heterogeneity. ► Considers the utility of orthosteric and allosteric ligands acting at NMDARs. ► Potential of the NMDAR C-terminal domain as a novel therapeutic target is discussed.
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影响因子：
5.5
作者：
Chen, Philip E.;Geballe, Matthew T.;Wyllie, David J. A.
通讯作者：
Wyllie, David J. A.
影响因子：
3.4
作者：
Amico-Ruvio, Stacy A.;Popescu, Gabriela K.
通讯作者：
Popescu, Gabriela K.
影响因子：
3.6
作者：
Burger, Pieter B.;Yuan, Hongjie;Traynelis, Stephen F.
通讯作者：
Traynelis, Stephen F.
DOI：
10.1073/pnas.1113761109
发表时间：
2012-02-28
影响因子：
11.1
作者：
Bach, Anders;Clausen, Bettina H.;Stromgaard, Kristian
通讯作者：
Stromgaard, Kristian
影响因子：
16.2
作者：
Beck, C;Wollmuth, LP;Kuner, T
通讯作者：
Kuner, T